Isolation, Characterization, and Unlocking the Potential of Mimir124 Phage for Personalized Treatment of Difficult, Multidrug-Resistant Uropathogenic E. coli Strain DOI Open Access
Alla K. Golomidova, Yu A Kupriyanov,

Ruslan Gabdrakhmanov

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12755 - 12755

Published: Nov. 27, 2024

Escherichia coli and its bacteriophages are among the most studied model microorganisms. Bacteriophages for various E. strains can typically be easily isolated from environmental sources, many of these viruses harnessed to combat infections in humans animals. However, some relatively rare pose significant challenges finding suitable phages. The uropathogenic strain UPEC124, a patient suffering neurogenic bladder dysfunction, was found resistant all coliphages our collections, initial attempts isolate new phages failed. Using an improved procedure phage enrichment, we N4-related Mimir124, belonging Gamaleyavirus genus, which able lyse this “difficult” strain. Although Mimir124 is narrow-spectrum phage, it effective individualized treatment patient, leading pathogen eradication. primary receptor O antigen O101 type; consequently, Mimir124-resistant clones were rough (having lost antigen). These clones, however, gained sensitivity that recognize outer membrane proteins as receptors. Despite presence nine potential antiviral systems genome UPEC124 strain, difficulty largely due efficient, non-specific cell surface protection provided by antigen. results highlight importance approach therapy, where narrow host-range phages—typically avoided pre-fabricated cocktails—may instrumental. Furthermore, study illustrates how integrating genomic, structural, functional insights guide development innovative therapeutic strategies, paving way broader applications therapy combating multidrug-resistant bacterial pathogens.

Language: Английский

Evolution and ecology of anti-defence systems in phages and plasmids DOI Creative Commons
Théophile Niault, Stineke van Houte, Edze R. Westra

et al.

Current Biology, Journal Year: 2025, Volume and Issue: 35(1), P. R32 - R44

Published: Jan. 1, 2025

Language: Английский

Citations

1
Structure and Activation Mechanism of a Lamassu Phage Defence System DOI Creative Commons
Yan Li, David W. Adams, Hon Wing Liu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Summary Lamassu is a diverse family of defence systems that protect bacteria, including pandemic strains Vibrio cholerae , against phage infection. They target essential cellular processes, aborting infection and preventing propagation by terminating the infected host. The mechanisms which efectors are activated when needed otherwise suppressed unknown. Here, we present structures system from Salmonella enterica . We show an oligomerization domain nuclease efector, LmuA, sequestered two tightly-folded SMC-like LmuB protomers LmuC. Upon activation, liberated LmuA proteins assemble into cyclic homo-tetramer, in four domains brought proximity to create active site capable cleaving DNA. propose tetramer formation likely one-way switch establishes threshold limit potential spontaneous activation cell death. Our findings reveal mechanism defence, involving liberation immune efectors, shed light on how balance potent responses with self-preservation.

Language: Английский

Citations

1
Going viral: The role of mobile genetic elements in bacterial immunity DOI
Beatriz Beamud, Fabienne Benz,

David Bikard

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(6), P. 804 - 819

Published: June 1, 2024

Language: Английский

Citations

8
Phage-induced efflux down-regulation boosts antibiotic efficacy DOI Creative Commons

Samuel Kraus,

Megan Fletcher,

Urszula Łapińska

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(6), P. e1012361 - e1012361

Published: June 28, 2024

The interactions between a virus and its host vary in space time are affected by the presence of molecules that alter physiology either or virus. Determining molecular mechanisms at basis these is paramount for predicting fate bacterial phage populations designing rational phage-antibiotic therapies. We study stationary phase Burkholderia thailandensis ΦBp-AMP1. Although heterogeneous genetic resistance to rapidly emerges B. , enhances efficacy three major antibiotic classes, quinolones, beta-lactams tetracyclines, but antagonizes tetrahydrofolate synthesis inhibitors. discovered enhanced facilitated reduced efflux phage. This new therapy allows eradication bacteria, whilst requiring concentrations, which crucial treating infections sites where it difficult achieve high concentrations.

Language: Английский

Citations

5
Invasive bacteriophages between a bell and a hammer: a comprehensive review of pharmacokinetics and bacterial defense systems DOI Creative Commons

Mohammed F Hamdi,

Alyaa Abdulhussein Alsaedi,

Alaa Qasim Hayder

et al.

Discover Life, Journal Year: 2025, Volume and Issue: 55(1)

Published: April 3, 2025

Language: Английский

Citations

0
Kiwa rescues RecBCD for anti-phage activity DOI Creative Commons
Zhiying Zhang,

Thomas C. Todeschini,

Yi Wu

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 26, 2023

Bacteria and archaea deploy diverse, sophisticated defence systems to counter virus infection, yet many immunity mechanisms remain poorly understood. Here, we characterise the Kiwa system as a membrane-associated supercomplex that senses changes in membrane induced by phage infection plasmid conjugation. This supercomplex, comprising KwaA tetramers bound KwaB dimers, its basic repeating unit, detects structural stress via KwaA, activating KwaB, which binds ejected DNA through DUF4868 domain, stalling replication forks thus disrupting late transcription. We show phage-encoded mimic protein Gam, inhibits RecBCD, also targets recognition. However, Gam binding one precludes inhibition of other. These findings reveal distinct mechanism bacterial immune coordination, where sensing disruptions inhibitor partitioning enhance protection against phages plasmids.

Language: Английский

Citations

4
The SAVED domain of the type III CRISPR protease CalpL is a ring nuclease DOI Open Access
Sophie C. Binder, Niels Schneberger, Marianne Engeser

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

Abstract Prokaryotic CRISPR-Cas immune systems detect and cleave foreign nucleic acids. In type III systems, the Cas10 subunit of activated recognition complex synthesizes cyclic oligoadenylates (cOAs), second messengers that activate downstream ancillary effector proteins. Once viral attack has been weathered, elimination extant cOA is essential to limit antiviral response allow cellular recovery. Various families ring nucleases have identified, specializing in degradation cOAs either as standalone enzymes or domains Here we describe nuclease activity inherent SAVED domain cA 4 -activated CRISPR Lon protease CalpL. We characterize kinetics cleavage identify key catalytic residues. demonstrate -incuced oligomerization CalpL not only for activation protease, but also required activity. Further, poses a limitation reaction, indicating mechanism regulation CalpL/T/S signaling cascade. This work first demonstration gives new insights into dynamics transcriptional adaption defense which are aimed at abortive infection rather reversible phage attack.

Language: Английский

Citations

1
The SAVED domain of the type III CRISPR protease CalpL is a ring nuclease DOI Creative Commons
Sophie C. Binder, Niels Schneberger, Maximilian Schmitz

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(17), P. 10520 - 10532

Published: Aug. 21, 2024

Abstract Prokaryotic CRISPR-Cas immune systems detect and cleave foreign nucleic acids. In type III systems, the Cas10 subunit of activated recognition complex synthesizes cyclic oligoadenylates (cOAs), second messengers that activate downstream ancillary effector proteins. Once viral attack has been weathered, elimination extant cOA is essential to limit antiviral response allow cellular recovery. Various families ring nucleases have identified, specializing in degradation cOAs either as standalone enzymes or domains Here we describe nuclease activity inherent SAVED domain cA4-activated CRISPR Lon protease CalpL. We characterize kinetics cA4 cleavage identify key catalytic residues. demonstrate cA4-induced oligomerization CalpL not only for activation protease, but also required activity. Further, poses a limitation reaction, indicating mechanism regulation CalpL/T/S signaling cascade. This work first demonstration gives new insights into dynamics transcriptional adaption defense systems.

Language: Английский

Citations

1
CRISPR/Cas9-Based Genome Editing of Fall Armyworm (Spodoptera frugiperda): Progress and Prospects DOI Creative Commons

Yussuf Mohamed Salum,

Anyuan Yin,

Uroosa Zaheer

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(9), P. 1074 - 1074

Published: Aug. 27, 2024

The fall armyworm (Spodoptera frugiperda) poses a substantial threat to many important crops worldwide, emphasizing the need develop and implement advanced technologies for effective pest control. CRISPR/Cas9, derived from bacterial adaptive immune system, is prominent tool used genome editing in living organisms. Due its high specificity adaptability, CRISPR/Cas9 system has been various functional gene studies through knockout applied research engineer phenotypes that may cause economical losses. practical application of diverse insect orders also provided opportunities developing strategies genetic control, such as drive precision-guided sterile technique (pgSIT). In this review, comprehensive overview recent progress S. frugiperda presented. We outline fundamental principles applying embryonic microinjection highlight study genes associated with biological aspects, including body color, insecticide resistance, olfactory behavior, sex determination, development, RNAi. ability technology induce sterility, disrupt developmental stages, influence mating behaviors illustrates roles management strategies. Furthermore, review addresses limitations studying function explores future potential promising controlling pest.

Language: Английский

Citations

1
Phage CRISPR-like regulatory RNAs silence bacterial adaptive and innate immunity DOI Open Access

Chao Liu,

Rui Wang, Zhihua Li

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 30, 2024

Abstract In prokaryotes, arrayed CRISPR RNAs (crRNAs) guide Cas proteins to destroy phage DNA/RNA, while solitary crRNA-like (crlRNAs) program for auto-regulation or control abortive infection (Abi)-inducing toxins that activate when CRISPR-Cas fails. Here, we report phages exploit crlRNA mimics hijack these multi-layered host defenses. Pseudomonas aeruginosa use crlRNAs thwart immunity by inhibiting expression, block Abi silencing an unprecedented RNA toxin features consecutive proline codons. Remarkably, the anti-CRISPR protein AcrIF24 selectively inhibits loaded with crRNAs/crlRNAs, allowing those complexed viral synergistically responses, as have co-adaptively evolved shorter spacer sequences. Furthermore, frequently organize multiplexed arrays, mirroring architecture of bacterial CRISPRs. Our findings showcase how silence defenses, and highlight delicate synergy between protein-based strategies.

Language: Английский

Citations

0